Resting membrane potential is created by an unequal distribution of ions across the plasma membrane, with the interior of the cell being more negatively charged than the exterior. 

The two main factors that determine the Resting membrane potential are: 

• The differences in ion concentration between the interior and exterior cellular environments
• The variable permeability of the cell membrane to different ion species

Because sodium, potassium, and chloride ions are present in the highest concentrations, these three ions have a major impact on the generation of Resting membrane potential.